The following discussion of the background of the invention is merely provided to aid the reader in understanding the invention and is not admitted to describe or constitute prior art to the present invention.
Hepatocellular carcinoma (HCC), the fifth most common solid tumor in the world, has shown a rising trend in terms of both incidence and mortality in the United States. These increases are largely associated with cirrhosis due to chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, alcohol abuse, and other causes. Current diagnosis of HCC in patients with clinical suspicion is based on imaging technology, serum alpha-fetoprotein (AFP) levels, and histology. These diagnostic tools have variable effectiveness for early diagnosis of HCC; cross-sectional imaging typically detects only tumors greater than 1 cm in diameter, and serological studies also lack sensitivity and specificity in patients with small tumors. Consequently, most cases of HCC are diagnosed in an advanced state when treatment options are limited.
MicroRNAs (miRNAs) are non-coding RNAs of 19-25 nucleotides in length that regulate gene expression by inducing translational inhibition or cleavage of their target mRNA through base pairing to partially or fully complementary sites. The miRNAs are involved in important biological processes, including development, cell differentiation, apoptosis and proliferation. miRNAs are also aberrantly expressed in several cancers, suggesting that they may have both oncogenic and tumor suppressor activities.